A5056759100- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Autism Spectrum Disorder Research
- Mitochondrial Function and Pathology
- Tuberous Sclerosis Complex Research
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Sexual Differentiation and Disorders
- Biochemical and Molecular Research
- Cellular transport and secretion
- Genetics, Bioinformatics, and Biomedical Research
- Ion Transport and Channel Regulation
- Genetics, Aging, and Longevity in Model Organisms
- Neurobiology and Insect Physiology Research
- Biotin and Related Studies
- Genetic factors in colorectal cancer
- Neurogenetic and Muscular Disorders Research
- Ethics in Clinical Research
- Biomedical Text Mining and Ontologies
- Erythrocyte Function and Pathophysiology
- Diabetes Treatment and Management
- Genomic variations and chromosomal abnormalities
- Genetic and Kidney Cyst Diseases
Greenwood Genetic Center
2021-2024
Children's Mercy Hospital
2018
University of Kansas
2013
We report for the first time, use of clinical genome sequencing (GS) in an unbiased pediatric cohort. describe validation, patient metrics, ordering patterns, results, reimbursement, and physician retrieval results consecutive 80 cases.Clinical GS was performed both inpatients outpatients undergoing etiologic evaluations. Results were reported electronic medical record. Evidence by clinicians whether interpretation concordant with laboratory obtained through retrospective chart review.Twenty...
PurposePathogenic variants in genes involved the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes regulator and mouse models suggest important role during development. We set out to determine whether KDM2B associated with NDD.MethodsThrough international collaborations, we collected data on individuals heterozygous variants. applied methylation arrays peripheral blood DNA samples a signature.ResultsWe recruited total 27...
Abstract Background Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the gene subject to X‐chromosome inactivation (XCI), factors including genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute clinical severity individuals RTT. Methods We analyzed patterns from blood samples 320 their mothers. It includes RTT ( n = 287) other syndromes sharing overlapping phenotypes (such as CDKL5 Deficiency...
X chromosome inactivation patterns may be clinically useful in assessing tumor clonality, determining carrier status for certain X-linked disorders, and evaluating the pathogenicity of a genetic variant identified an gene. The protocols this article utilize highly polymorphic trinucleotide repeat within first exon human androgen receptor gene (AR) methylation-sensitive restriction enzyme HpaII to distinguish between maternal paternal alleles simultaneously determine their methylation status....
Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, disease causing MECP2 allele resides on paternal X chromosome while healthy copy maintained maternal with inactivation (XCI) resulting mosaic expression of one each cell. Preferential theorized to result reduced severity; however, establishing such correlation complicated known genotype...
Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, disease causing MECP2 allele resides on paternal X chromosome while healthy copy maintained maternal with inactivation (XCI), resulting mosaic expression of one each cell. Preferential theorized to result reduced severity; however, establishing such correlation complicated known genotype...
The variable evidence supporting gene–disease associations contributes to the difficulty of accurate variant reporting in a clinical setting. An evidence-based scoring system for evaluating validity associations, proposed by ClinGen, considers experimental as well genetic evidence. De novo variants are heavily weighted, given overall rarity genome and their contribution human disease, however they reported "genes unknown significance" our center when there is insufficient assertion. We...
Ankyrins are a family of proteins that link integral membrane to the underlying spectrin-actin cytoskeleton and play key role in activities such as cell motility, activation, proliferation, cell–cell contact, maintenance specialized domains. Ankyrin 3 (ANK3) is one three major subtypes ankyrin protein family. Ankryin genes ubiquitously expressed, but their expression highest brain. In central nervous system, ankyrins have critical roles at axonal initial segment, nodes Ranvier, synapses. To...
Abstract Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl‐CpG‐binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most RTT‐causing MECP2 de novo usually on the paternally inherited X chromosome. While paternal age has been reported to be associated increased risk genetic disorders, it unknown whether parental contributes development Clinical data including age, RTT diagnostic status, clinical severity collected...
Variants in the X-linked gene AIFM1 (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. encodes mitochondrial flavin adenine dinucleotide (FAD)-dependent nicotinamide (NADH) oxidoreductase, roles regulation of respiratory complex assembly function, production reactive oxygen species, coordination caspase-independent type apoptosis...
HSD10 disease is a rare X-linked mitochondrial disorder caused by pathogenic variants in the HSD17B10 gene. The phenotype results from impaired 17β-hydroxysteroid dehydrogenase 10 (17β-HSD10) protein structure and function. multifunctional involved enzymatic degradation of isoleucine branched-chain fatty acids, metabolism sex hormones neurosteroids, as well regulating RNA maturation. characterised progressive neurologic impairment. Disease onset varied includes neonatal-onset,...
De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of transcription factor deformed epidermal autoregulatory 1 (DEAF1) result a phenotypic spectrum disorders termed DEAF1-associated neurodevelopmental (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion Deaf1 central nervous system indicate that loss activity results altered expression genes involved neuronal function, dendritic spine maintenance, development, activity, reduced...
Prader-Willi syndrome (PWS) and Angelman (AS) are genomic imprinting disorders, mapped to chromosome 15q11.2-q13, which caused by copy number changes, uniparental disomy of 15 (UPD15), center (IC) defects in the critical region, single nucleotide variants. Therefore, establishing or ruling out a molecular diagnosis PWS/AS presents unique challenges due various genetic etiologies. The Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) kit (MRC Holland) is...
RORA encodes the RAR-related orphan receptor-α (RORα), playing a pivotal role in cerebellar maturation and function. Here, we report largest series of individuals with RORA-related-neurodevelopmental disorder (RORA-NDD). Forty (30 unrelated; 10 siblings from 4 families) carrying pathogenic/likely pathogenic variants were collected through an international collaboration. The 33 (29 de novo, inherited, one shared), identified by genome/exome sequencing (n=21), chromosomal-microarray-analysis...